RU2241002C1 - 1,2,3,4-tetrahydropirido[3',2':4,5]thieno-[3,2-d]-pyrimidin-4-ones as antidotes of herbicide with hormonal effect of 2,4-dichlorophenoxyacetic acid - Google Patents

Abstract

FIELD: organic chemistry.

SUBSTANCE: invention describes 1,2,3,4-tetrahydropyrido[3',2':4,5]thieno-[3,2-d]-pyrimidin-4-ones of the formula (1):

wherein (1a) R means 5-bromofuryl-2; (1b) R means furyl-2; (1c) R means cyclohexyl. Invention provides preparing new compounds used in agriculture in aim for protection of agricultural crops against negative effect of 2,4-dichlorophenoxyacetic acid.

EFFECT: valuable properties of compounds.

1 tbl, 4 ex

Description

The invention relates to new chemical biologically active substances from a number of heterocyclic compounds of the formula (1a-b),

where (1a) R = 5-bromofuryl-2; (1b) R = furyl-2; (1c) R = cyclohexyl,

exhibiting the property of weakening the toxic effect of the hormonal herbicide of 2,4-dichlorophenoxyacetic acid (2,4-D) on sunflower seedlings.

The antidote activity against 2,4-D is possessed by 2- (n-aminobenzenesulfamido) -5-ethyl-1,3,4-thiadiazole of the formula (2), adopted as a prototype according to the properties (patent No. 2040898 Antidote of the hormonal action herbicide 2 , 4-dichlorophenoxy-acetic acid // Strelkov V.D., Isakova L.I., Kalita M.I., Litvinova L.N., Chubenko T.I. MKI A 01 N 25/32, 43/82, publ. 09.08.95. BI No. 22).

The structural analogue of the synthesized compounds (1a-b) can be 3-amino-6-methyl-4-methoxymethyl-2- (4-nitrophenyl) thieno [2,3-b] pyridine (3)

[Ye. A. Kaigorodova, V.K. Vasilin, L.D. Konyushkin, Ye.B. Usova, G. D. Krapivin Synthesis and Reactions of Substituted 3-amino-2-furyl (benzyl) -hieno [2,3-b] pyridines // Molecules. 2000. - No. 5. -P.1085-1093 // http://www.mdpi.org.

The objective of the present invention is to expand the arsenal of biologically active substances obtained synthetically for use in agriculture to protect crops from the negative effects of herbicides.

This is achieved by using 1,2,3,4-tetrahydropyrido [3 ’, 2’: 4,5] thieno [3,2-d] pyrimidin-4-ones (1a-b) by treating the germinated sunflower seeds.

Compounds (1a-c) were obtained by the condensation reaction of 3-amino-6-methyl-4-methoxymethylthieno [2,3-b] pyridin-2-carboxamide 4 with aldehydes in toluene in the presence of n-toluenesulfonic acid:

(1a) R = 5-bromofuryl-2; (1b) R = furyl-2; (1c) R = cyclohexyl.

The invention is illustrated by the following examples.

Example 1. Obtaining 6-methyl-4-methoxymethyl-2- (5-bromofuryl-2) -1,2,3,4-tetrahydropyrido [3 ', 2': 4,5] thieno [3,2-d] pyrimidin-4-one (1a)

2.5 g (0.01 mol) of thienopyridine 4 was dissolved in 50 ml of toluene, 1.92 g (0.011 mol) of 5-bromofurfural was added and then n-toluenesulfonic acid was added at the tip of the spatula. The reaction mixture was boiled under reflux for 3 hours, after which the solvent was evaporated by a third. The crystalline precipitate was separated and washed with 10 ml of cold ethanol. Recrystallized from dimethylformamide. The yield of compound (1a) was 3.4 g (83%). _Mp = 210-212 ° C (decomp.).

Elemental analysis for C ₁₆ H ₁₄ BrN ₃ O ₃ S: Found,%: C 47.17; H 3.44; N, 10.26. Calculated,%: C 47.07; H 3.46; N, 10.29. ¹ H NMR spectrum (DMSO-d ₆ , 500 MHz): 2.58 (3H, s, CH ₃ ), 3.42 (3H, s, OCH ₃ ), 4.83 (2H, s, OCH ₂ ), 5.87-5.94 (1H, m, CH), 6.30 (1H, d, 3-H _Fur ³ J = 3.4 Hz), 6.37 (1H, d, 4-H _Fur , ³ J = 3.4 Hz), 6.98 (1H, d, NH _Amide , J = 3.4 Hz), 7.17 (1H, s, N _Ru ), 8.2 (1H, br.s, NH _Amin ). Mass spectrum, m / z (relative peak intensity in% of maximum): 407 (48), 328 (88), 296 (12), 235 (100), 219 (98), 203 (27), 175 (27 ), 163 (21), 42 (20), 39 (16).

Example 2. Obtaining 6-methyl-4-methoxymethyl-2- (furyl-2) -1,2,3,4-tetrahydropyrido [3 ', 2': 4,5] thieno [3,2-d] pyrimidine- 4-she (1b)

2.5 g (0.01 mol) of thienopyridine 4 was dissolved in 50 ml of toluene, 0.9 ml (0.011 mol) of furfural was added, and then n-toluenesulfonic acid was added at the tip of the spatula. The reaction mixture was boiled under reflux for 3 hours, after which the solvent was evaporated by a third. The crystalline precipitate was separated and washed with 10 ml of cold ethanol. Recrystallized from dimethylformamide. The yield of compound (1b) was 2.57 g (78%). _Mp = 259-260 ° C.

Elemental analysis for C ₁₆ H ₁₅ N ₃ O ₃ S: Found,%: C 58.47; H 4.56; N, 12.70. Calculated,%: C 58.35; H 4.59; N, 12.76. ¹ H NMR spectrum (DMSO-d ₆ , 500 MHz): 2.57 (3H, s, CH ₃ ), 3.39 (3H, s, OCH ₃ ), 4.85 (2H, s, OCH ₂ ), 5.93-5.99 (1H, m, CH), 6.30-6.35 (2H, m, 3.4-H _Fur ), 6.99 (1H, d, NH _Amide , J = 3, 4 Hz), 7.24 (1H, s, N _Ru ), 7.55 (1H, d, 5H _Fur , J = 1.8), 8.21 (1H, br.s, NH N _amine ).

Mass spectrum, m / z (relative peak intensity in% of maximum): 329 (83), 312 (13), 296 (18), 235 (100), 230 (10), 219 (89), 203 (25 ), 175 (23), 163 (22), 135 (10), 94 (22), 73 (23), 42 (21), 39 (27).

Example 3. Obtaining 6-methyl-4-methoxymethyl-2-cyclohexyl-1,2,3,4-tetrahydropyrido [3 ', 2': 4,5] thieno [3,2-d] pyrimidin-4-one ( 1c)

2.5 g (0.01 mol) of thienopyridine (4) was dissolved in 50 ml of toluene, 1.3 ml (0.011 mol) of cyclohexanecarbaldehyde was added and then n-toluenesulfonic acid was added at the tip of the spatula. The reaction mixture was boiled under reflux for 3 hours, after which the solvent was evaporated by two-thirds, the residue was diluted with 20 ml of petroleum ether. The resulting precipitate was separated and recrystallized from ethanol. The yield of compound (1b) was 2.56 g (74%). _Mp = 225-226 ° C.

Elemental analysis for C ₁₈ H ₂₃ N ₃ O ₂ S: Found,%: C 62.72; H, 6.67; N, 12.11. Calculated,%: C 62.58; H 6.71; N, 12.16. ¹ H NMR spectrum (DMSO-d ₆ , 500 MHz): 1.08-1.92 (10H, m, H _cg ), 2.61 (3H, s, CH ₃ ), 3.41 (3H, s, OCH ₃ ), 4.78 (2H, s, OCH ₂ ), 4.52-4.58 (1H, m, CH), 6.28 (1H, d, NH _Amide , J = 3.4 Hz), 7.09 (1H, s, N _Ru ); 7.54 (1H, br.s, NH N _amine ).

Mass spectrum, m / z (relative peak intensity in% of maximum): 345 (65), 262 (17), 296 (18), 235 (100), 230 (10), 219 (92), 203 (25 ), 175 (23), 163 (22), 94 (34), 73 (33), 42 (29), 39 (33).

Example 4. The study of the antidote activity of 1,2,3,4-tetrahydropyrido [3 ', 2': 4,5] thieno [3,2-d | pyrimidin-4-ones (1a-b) to 2,4- D

Antidote activity of 1,2,3,4-tetrahydropyrido [3 ', 2': 4,5] thieno [3,2-d] pyrimidin-4-ones (1a-c) to 2,4-D 500 BP BASFAG (GR No. 582313-1) was studied in laboratory conditions on seedlings of sunflower cultivar VNIIMK-8883. The inventive compounds, the prototype according to the property of 2- (n-aminobenzenesulfamido) -5-ethyl-1,3,4-thiadiazole and the analogue in structure (3) were tested in the form of solutions, the alcohol content was 0.2%, the content of the claimed compound and the prototype was 10 ^-2 -10 ^-5 % (by weight).

Sprouted sunflower seeds were exposed to 2,4-D and an antidote. Some seeds were treated only with herbicide (reference standard). The control was seeds treated with water. Further seed germination was carried out at a temperature of 28 ° C for 3 days, the length of the hypocotyl and the root of sunflower seedlings were measured.

Antidote activity was evaluated by increasing the length of the root and hypocotyl of the seedlings in the herbicide + antidote variant as compared with the herbicidal variant (reference). In parallel, a prototype test of -2- (n-aminobenzenesulfamido) -5-ethyl-1,3,4-thiadiazole and an analogue in structure was carried out (3).

Statistical processing of experimental data was carried out using t-student test at a probability level of P = 0.95. The test results are presented in the table.

As follows from the table, the claimed compounds (1A-C) reduce the toxicity of 2,4-D for seedlings of sunflower, exceeding the prototype (2) and analogue in structure (3). So, the compound (1a) in the optimal concentration of 10 ^-2 % increases the length of the hypocotyl by 23%, the root - by 30% in comparison with 2,4-D. Compound (1b) in an optimal concentration of 10 ^-3 % increases the length of the hypocotyl by 23%, the root - by 37% compared with 2,4-D. Compound (1c) in an optimal concentration of 10 ^-2 % increases the length of the hypocotyl by 23%, the root - by 40% compared with 2,4-D. While the prototype (2) in an optimal concentration of 10 ^-3 % increases the length of the hypocotyl by 9% and the length of the root by 28% compared to 2,4-D.

The analogue in structure (3) at an optimal concentration of 10 ^-3 % increases the length of the hypocotyl by 3%, the root - by 16% with respect to 2,4-D.

Thus, compounds (1a-c) exhibit antidote properties and can be used in agricultural practice to relieve the toxic effects of 2,4-D herbicide on plants and activate their growth.

Claims (1)

1,2,3,4-Tetrahydropyrido [3'2 ': 4,5] thieno [3,2- d ] pyrimidin-4-ones of formula 1

la R = 5-bromofuryl-2; 1b R = furyl-2; 1 in R = cyclohexyl, exhibiting antidote activity to the herbicide of the hormonal action of 2,4-dichlorophenoxyacetic acid on sunflower seedlings.